Provenge-1

Information about the trial can be found at: www.dendreon.com which explains the theory behind using dendritic cells to train the T-cells to seek out and destroy PC cells. The immune system normally ignores them because it identifies them as part of the body.

Unlike vaccines we are familiar with (smallpox, polio, measles, etc.) which protect against diseases you are exposed to, Provenge is designed to initiate the immune response to intracellular abnormalities caused by viruses, some bacteria, and cancers.

The treated dendritic cells activate T-Cells to attack and kill the cancer cells. These activated T-Cells survive and continue to recognize their target antigen. This vaccine approach is expected to have a long lasting therapeutic effect. (This is logical, since recent reports say that it is expected that even those of us vaccinated against smallpox 40 years ago or so should still have at least some protection today.)

According to Dr. Valone’s presentation at the year 2000 PCRI Conference, of the 100 patients they had treated to that time, better than 80% had no side effects at all. The most severe were similar to the reaction one gets from a flu shot, and lasted only a day or two.

For the trial, 2/3 of the participants receive the vaccine and 1/3 get a placebo. If anyone progresses on the placebo, he is given the option of participating in a follow-up trial in which he receives the vaccine. [Dendritic cells have been frozen and saved for this potentiality.] This "2nd chance" provision was a major reason I was willing to participate. Also, no matter how my numbers & tests have fluctuated over the years, I'm still feeling physically fine -- "If I didn't KNOW I had this disease, I WOULDN'T know I had it." [Also why I've been willing to try some "off-the-wall" therapies.] See below.

Now, we all know that NOTHING works for EVERYONE. So, whether this will help me or not, I don’t know—but I think it’s worth a shot.

After a failed radical prostatectomy in 1992, resulting in a metastasis on my left scapula, CHT worked for me for about 3-1/2 years. PSA nadir was 0.2, from which it started to rise.

At PSA 34.1, I started 2^nd line hormonal treatments with Cytadren and Hydrocortisone, which worked for another 3 years or so. Nadir was 5.3.

Since then I have tried Rife/Bare, PC SPES, Carnivora, GCP, and GCP with AHCC. None of them stemmed the rising tide of PSA, which currently is 34.5.

However, my QOL is quite good. The met gives me no pain or discomfort, and bone scans have shown it to be “stable” for the past 4 years. I tell people that if I didn’t KNOW I had this disease, I WOULDN’T know I had it. I attribute at least some of this situation from radical diet change and addition of beneficial supplements, etc. that we all know about.

But, I do know I do. And because it’s like the proverbial sword of Damocles over my head, I am hoping to be accepted for the Provenge trial.

I do believe that a cure (or permanent control, which to my mind is just as good), whether from vaccines, anti-angiogenesis, gene therapy, or whatever is in the offing, and I plan to stick around until answers are found.

My tea tag this afternoon says: “Not everything that is faced can be changed, but nothing can be changed unless it is faced.”

Here’s How Things Went as I Explored Entering the Provenge trial and events after acceptance and entry into the Provenge trial:

Eligibility:

1. Prostate cancer that has spread outside the prostate gland

2. Disease progression despite treatment with hormone therapy

3. No cancer-related pain

4. A rising PSA

After preliminary interview at a local site, data is submitted to Dendreon. Prior to this interview, I provided my PCa history, copies of the pathology reports from the biopsy and from the surgery, and copies of my last 2 PSA reports. At the end of this interview with the Clinical Research Coordinator, she expressed the opinion that I am an excellent candidate. If I’m accepted, we’re aiming at a January-February 2002 time frame for the procedures.

The Clinical Research Coordinator is in contact with the hospital where I had the RRP to obtain pathology slides, etc.

To determine final acceptance, I will have a physical exam, blood tests, urinalysis, an EKG, a chest X-ray, a bone scan, and a CT scan or MRI. If you are accepted, you are randomized to receive the treatment (2 of 3) or a placebo. If my condition worsens on the placebo, I will be offered the opportunity to enter a follow-up trial with the active vaccine.

The coordinator told me that we probably will not know the final decision until about a week or so before the start of the procedure.

Here's how things looked before and during the procedure(s).

1. Provide PCD, last few PSA reports, recent scans, pathology reports from surgery, permission for them to borrow films, etc .

2. When still eligible, submit to baseline tests: Bone Scan, CT Scan, blood tests, Chest X-Ray, EKG. These were done at Riverside Memorial Hospital in Columbus (the only Ohio site for the trial) on 12/27 &12/28/01. Following this, and providing a couple of other clarifications, I was accepted for the trial.

3. Blood cells will be removed from me by leukapheresis—the blood flows from a vein in one arm to a machine where immature dendritic cells and mononuclear cells are removed and saved, and the rest of the blood flows back into a vein in my other arm.

On 1/8/02 I went in for the leukapharesis procedure. You lie still & can't move your arms during the process, which in my case lasted about 2-1/2 hours. It really wasn't too bad. My wife was at bedside & able to feed cassettes into a portable player so I could listen to jazz during the time, I could talk to her, and also the ones performing the procedure.

4. The dendritic cells are then treated with a prostate tumor protein for 40 hours to produce the vaccine. (If I’m in the placebo group, dendritic cells will be frozen and saved for possible future use.)

They Fed Ex the product to a processing center -- in my case I believe it was in Philadelphia -- where the vaccine is prepared over a period of 40 hours. On 1/10/02 I returned to Columbus in the afternoon, and when the vaccine (or placebo) arrived, it was infused back into me. This takes about a half hour.

On Monday afternoon (1/13) I returned to Columbus for an appointment with the Doc conducting the trial and blood tests.

5. The same procedures (physical exam, blood tests, leukapheresis, and infusion) will be repeated two weeks and four weeks after the first treatment. That ends the treatment cycle.

This same series was repeated on 1/22, 24, & 27 and 2/5, & 2/7. The therapy portion of the trial was complete at this point -- Dendreon feels that 3 cycles is optimum to "train" the dendritic & T-cells, and that they will survive and remember permanently.

5. Physical exams and blood tests to monitor condition and look for treatment complications will be repeated at weeks 8, 12, 16, 24, 32, and the every 12 weeks after starting treatment.

On 2/28 I returned to Columbus for a bone scan. (Didn't need a CT scan because my baseline CTs were clear.) This was a week early on the published schedule but we wanted to leave for Florida the next day, and there is a 7 day window, so I was allowed to do it then.

6. Participants are followed for 3-1/2 years, according to the consent form, so I will be returning periodically for bone scans and blood work. The trial is "no cost" to the patient -- but of course they do send claims to medicare and secondary insurance carriers. Whatever they won't pay, Dendreon does.

First Results!

From: Jack M. Beaven [mailto:mahlonbeav@juno.com]
Sent: Monday, March 18, 2002 6:55 PM
To: hrpca@yahoogroups.com
Subject: [hrpca] Re: Dendreon/Provenge Phase III trial

Hi to the group:

Today I received the report from the first post-treatment bone scan. It was compared to the baseline scan done on 12/27/01.

Essentially, the "Opinion" stated that the comparison suggests improvement in the metastatic disease, with no new areas identified to suggest progression.

While it "takes more than one robin to make a spring," this result suggests (to me at least) that (1) I received the vaccine instead of a placebo, and (2) the vaccine is having a beneficial effect. I also think the fact that I had the scan on 2/28 (a week earlier than the "official" schedule) so we could come away to Florida -- giving the vaccine a little less time to take effect -- is a further positive sign.

While we're feeling pretty good about this report, we're not popping any champagne corks just yet. I'm sure not going to abandon my diet & supplements regime any time soon. :-)

My (green) tea tag tonight says: "Success is a journey, not a destination."

jack
~~~~~~~~~~~~~~~~~~~~~~~~~~~~
** Jack Beaven   *****   Dayton, Ohio **
******     MahlonBeav@juno.com     *****
** 10-year Prostate Cancer Survivor   **

Dendritic Cell Based Vaccines